tbuckley/cabot-search huggingface dataset:
Abstract 14: A Novel Pharmacologic Peptide Improved Survival And Neurologic Outcomes After Swine PEA
Authors: Matt T Oberdier, Jing Li, Daniel Ambinder, Masahito Suzuki, Ethan Tumarkin, Sarah Fink, Xiangdong Zhu, CODY JUSTICE, Terry L Vanden Hoek, Henry R Halperin
Journal: Circulation (2022)

Introduction: Successful outcomes following cardiac arrest and CPR are between 5 and 15%. No pharmacologic agent has been shown to improve survival with good neurologic function. A pharmacologic agent that favorably influences heart and brain metabolism following arrest would be ideal. Our group has produced a peptide, TAT-PHLPP9c, that enhances the activity of Akt by inhibiting PH domain leucine-rich repeat phosphatase (PHLPP). Activation of this pathway prevents cardiac stunning and cerebral edema by limiting the release of taurine and glutamate, respectively. Hypothesis: Neurologic outcomes following PEA arrest in swine will be improved by the administration of TAT-PHLPP9c during CPR. Methods: 24 female pigs (30-35 kg) were anesthetized, mechanically ventilated, and catheterized. Pulseless electrical activity (PEA) was induced by inflating balloons at proximal positions in the left anterior descending and right coronary arteries to full occlusion. After an average PEA period of 7 minutes, ACLS was initiated with mechanical ventilation and vest CPR. For the controls (n=12), boluses of 0.5 mg epinephrine were administered via the venous line after one and three minutes of support. For the peptide treated animals (n=12), boluses of 7.5 mg/kg TAT-PHLPP9c were also given at one and three minutes of CPR. The balloons were deflated and removed after two minutes of support. ACLS continued until ROSC was achieved. Animals were recovered post-anesthesia and classified as neurologically intact or not intact based on behavior norms for healthy pigs. Animals with ROSC that were neurologically intact were survived overnight. Results: ROSC was more common in the peptide group, but this difference was not significant (8 control versus 12 peptide, P=0.0932). Survival was significantly more frequent in the peptide group (0 control vs. 11 peptide, P&lt;0.00001), and all survivors were neurologically intact. Conclusion: Peptide administration during CPR is promising as a means of improving survival and neurologic outcomes following PEA arrest.
Abstract 13847: The Ross Procedure versus Mechanical versus Bioprosthetic Aortic Valve Replacement: A Network Meta-Analysis
Authors: Yujiro Yokoyama, Toshiki Kuno, Nana Toyoda, Tomohiro Fujisaki, Hisato Takagi, Shinobu Itagaki, Michael Ibrahim, Maral Ouzounian, Ismail El-Hamamsy, Shinichi Fukuhara
Journal: Circulation (2022)

Background: The Ross operation appears to restore normal survival in young and middle-aged adults with aortic valve disease. However, there is limited data comparing it to conventional aortic valve replacement options. Objectives: To compare outcomes of the Ross procedure, mechanical and bioprosthetic aortic valve replacement (M-AVR, B-AVR). Methods: MEDLINE and EMBASE were searched through March 2022 to identifyrandomized controlled trials (RCTs) and propensity-score matched studies (PSMs) that investigated outcomes of patients ≥16-year-old undergoing the Ross procedure, M-AVR or B-AVR. Result: The systematic literature search identified 2 RCTs and 8 PSMs involving a total of 4,812 patients (Ross: n=1,991; M-AVR: n=2,019; B-AVR: n=802). All-cause mortality was significantly lower in the Ross procedure group compared with M-AVR (hazard rate (HR) [95% confidence interval (CI)]=0.58 [0.35-0.97], P=0.035) and BAVR (HR [95% CI]=0.32 [0.18-0.59], P &lt;0.001) groups. The reintervention rate was lower in the Ross and M-AVR groups compared with B-AVR (HR [95% CI] =0.31 [0.15-0.65], P=0.002, HR [95% 272 CI] =0.15 [0.05-0.41], P&lt; 0.001, respectively), while it was higher after the Ross procedure compared with M-AVR group (HR [95% CI] =2.12 [1.04-4.33], P=0.039). However, post-Ross reinterventions included both autograft and right ventricular outflow tract. Major bleeding rate was lower after the Ross procedure compared with M-AVR. Long-term stroke rate was lower following the Ross procedure compared with M-AVR and B-AVR. The rate of endocarditis was also lower after the Ross procedure compared with B-AVR. Conclusion: Improved long-term outcomes of the Ross procedure are demonstrated compared with conventional M-AVR and B-AVR options. These results highlight a need to enhance the recognition of the Ross procedure and revisit current guidelines regarding the optimal valve substitute for young and middle-aged patients.
Abstract 13662: The Role of Pcsk9 in Abdominal Aortic Aneurysm
Authors: Yae Hyun Rhee, Joshua Spin, Alicia Deng, Colwyn Headley, Philip S Tsao
Journal: Circulation (2022)

Introduction: Abdominal aortic aneurysm (AAA) is a local weakening and dilatation of the abdominal aorta ≥50%, is associated with high mortality in the event of rupture and has no current pharmacologic treatment. Proprotein convertase subtilisin/kexin type 9 (Pcsk9), an enzyme mainly known for its production in liver, can cause familial hypercholesterolemia due to gain-of-function mutations. When triggered by pro-inflammatory stimuli, Pcsk9 expression by vascular smooth muscle cells (VSMC) has been found to induce cellular polyploidy, senescence, and apoptosis, hallmarks of AAA. Further, our collaborative consortium identified a relationship between Pcsk9 variants and AAA disease in humans utilizing a genome-wide association stud y (GWAS) in the Million Veteran Program. Lastly, our transcriptional profiling experiments in the porcine pancreatic elastase (PPE) model of murine AAA found significant early (Day 3) upregulation of the Pcsk9 gene in aorta.Monoclonal Pcsk9 antibody therapies are effective for hypercholesterolemic patients who are resistant to conventional statin therapy. However, the role of Pcsk9 in AAA has not been explored in depth. If Pcsk9 were found to be pivotal in disease, Pcsk9-inhibitors could be high priority candidates for investigation in limiting AAA. Methods: Using the PPE model, AAA was induced in wildtype C57Bl/6 mice and Pcsk9 knock-out (KO) mice. Aneurysm growth was monitored via sonography at various time points, and local vascular Pcsk9 and inflammatory marker gene expression were measured by qPCR. In vitro, VSMC were treated with exogenous Pcsk9 and assayed for pro-inflammatory marker expression. Results: Sonographic imaging data showed smaller AAA diameters in Pcsk9 KO mice compared with wildtype C57Bl/6 mice. Inflammatory gene expression was significantly downregulated with Pcsk9 KO. In-vitro VSMCs showed upregulated inflammation after exogenous Pcsk9 treatment. Conclusions: Our data suggest that Pcsk9 plays a crucial role in the development of AAA and could be a viable treatment target to inhibit AAA progression.
Ultraviolet-induced fluorescent dermoscopy for biopsy site identification prior to dermatologic surgery: A retrospective study
Authors: Cristian Navarrete-Dechent, Pawel Pietkiewicz, Stephen W. Dusza, Sebastian Andreani, Kishwer S. Nehal, Anthony M. Rossi, Miguel Cordova, Erica H. Lee, Chih-Shan J. Chen, Alvaro Abarzua-Araya, Pablo Uribe, Juan C. Castro, Katherine Droppelmann, Consuelo Cardenas, Ashfaq A. Marghoob
Journal: Journal of the American Academy of Dermatology (2023)
Abstract 13821: Genetic Identification of Homozygous Familial Hypercholesterolemia by Long-Read Sequencing Among Patients With Clinically Diagnosed Heterozygous Familial Hypercholesterolemia
Authors: Ahsen Chaudhry, Kristin Vesely, Lubomira Cermakova, Mark Trinder, Liam R Brunham
Journal: Circulation (2022)

Background: Homozygous Familial Hypercholesterolemia (HoFH) is a rare genetic disorder characterized by extremely elevated plasma low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerosis. Accurate identification of patients with HoFH is essential as they may be eligible for specialized treatments. The objective of this study was to identify and characterize patients with HoFH among patients with clinically diagnosed heterozygous FH (HeFH). Methods: We studied patients from the British Columbia FH Registry with a Dutch Lipid Clinic Network score ≥6 and no secondary cause of hypercholesterolemia. We performed targeted next-generation sequencing of the LDLR , APOB , PCSK9 and LDLRAP1 genes. Long-read sequencing of the LDLR gene was subsequently done for patients with &gt;1 pathogenic LDLR variant to determine haplotypes. We examined lipid levels and cardiovascular events (unstable angina, myocardial infarction and coronary revascularization). Results: Among 705 patients with clinically diagnosed HeFH, we identified a single pathogenic variant in 300 (42.6%) patients and &gt;1 pathogenic variant in the LDLR gene in 11 (1.6%) patients. We established a genetic diagnosis of HoFH in 6 (0.9%) patients (3 true homozygous and 3 compound heterozygous in trans). The mean baseline LDL-C of genetically identified HoFH patients was significantly higher than those with 1 variant. The prevalence of premature cardiovascular disease was numerically greater in the genetically identified HoFH group (29.4% vs 18.0%, p=0.2). Conclusions: In a cohort of patients with clinically diagnosed HeFH, genetic testing by long-read sequencing revealed that 0.9% had HoFH. These patients tended to have a more severe phenotype. Genetic testing of patients with clinical FH may identify patients with HoFH that had eluded clinical diagnosis.
Abstract 13988: A Devastating Case of Clostridial Infective Endocarditis
Authors: Faysal Alhasan, Nicholas Biondi, Nataly Akbarshahi, Blair Suter, Wisam Beauti, Jackson Walker, Andrew Hendrix, Mashhood Kakroo
Journal: Circulation (2022)

Introduction: Cardiac necrotizing soft tissue infections (NSTI) have been scarcely reported in the literature. We present a rare case of a disseminated NSTI with myocardial involvement secondary to embolic phenomena from emphysematous infective endocarditis (IE). Case presentation: 73-year-old female on dialysis with atrial fibrillation and diabetes mellitus was transferred for multifocal strokes evidenced on magnetic resonance imaging. Presented with leukocytosis, lactic acidosis, acute liver failure, and right upper extremity (RUE) NSTI. She was started on antibiotics and vasopressors and taken emergently to the operating room for RUE amputation. Following surgery, an electrocardiogram revealed anterior STEMI. Bedside transthoracic echocardiogram noted a severely reduced ejection fraction and a mitral valve vegetation. Computed tomography of head and chest revealed pneumomyocardium, portal venous gas, and pneumocephalus. Blood cultures revealed growth of Clostridium perfringens. With severe multi-organ failure and a poor prognosis, comfort care was elected, and the patient expired. Figures: A: RUQ subcutaneous gas. B: Chest wall gas. C: pneumocephalus. D: pneumomyocardium. E: MV vegetation. Discussion: Septic embolization is a devastating sequela of IE. Vegetations &gt; 1cm have increased embolic potential and all-cause mortality. The most common site of embolization is the central nervous system; however, coronary embolization can also occur. Clostridial endocarditis is rare, despite being documented as the first cause of anaerobic IE. Mortality rate of clostridial NSTI and shock exceeds 50%. Source control and rapid identification of infection are paramount for treatment success. A multidisciplinary approach should be employed when treating Clostridial infections, specifically endocarditis. Our case highlights the need for prompt recognition of IE and the interplay of multimodal imaging in the diagnosis of disseminated infection.
Additional neoadjuvant immunotherapy does not increase the risk of anastomotic leakage after esophagectomy for esophageal squamous cell carcinoma: a multicenter retrospective cohort study
Authors: Zhinuan Hong, Jinxin Xu, Zhen chen, Hui Xu, Zhixin Huang, Kai Weng, Junlan Cai, Sunkui Ke, Shuchen Chen, Jinbiao Xie, Hongbing Duan, Mingqiang Kang
Journal: International Journal of Surgery (2023)

Neoadjuvant chemoimmunotherapy (nICT) is a novel and promising therapy model for locally advanced esophageal squamous cell carcinoma.The objective of this study aimed to assessed the impact of additional neoadjuvant immunotherapy on patients' short-term outcomes, particularly the incidence of anastomotic leakage (AL) and pathological response.
Abstract 13200: Loss of Cardiomyocyte β2 Spectrin Promotes Cardiac Dyad Dysfunction and Accelerated Heart Failure
Authors: Shane S Scott, Ethan J Schwendeman, Anna Matzko, Mohamed H Derbala, Maciej Pietrzak, Xianyao xu, Jeffrey R Tonniges, Brandon J Biesiadecki, Peter J Mohler, Thomas J Hund, Sakima A Smith
Journal: Circulation (2022)

Background: The cardiac dyad and associated calcium (Ca 2+ ) release units (CRUs) are integral for cardiac excitation-contraction (E-C) coupling. The cardiac dyad is a multicomponent complex composed of the transverse-tubules, junctional sarcoplasmic reticulum (jSR), and CRU-associated proteins. Proper E-C coupling requires Ca 2+ influx via long-lasting-L-type Ca 2+ channels (Cav1.2), which triggers Ca 2+ release from adjacent ryanodine receptor 2 (RyR2) located in jSR. βII-spectrin loss alters RyR2 localization, but its contribution to cardiac dyad organization and E-C coupling remains unclear. Hypothesis: We hypothesized that βII-spectrin is required for cardiac dyad organization and proper cardiomyocyte calcium signaling. Methods: Cardiomyocyte-specific βII-spectrin knockout (βII-cKO) and control mice (βII-flox) were generated and harvested for immunoblotting, qRT-PCR, and imaging by transmission electron microscopy (TEM). Mice hearts were also interrogated by echocardiography following transaortic constriction. Results: Cardiac dyad structure and CRU components are significantly altered in βII-cKO hearts. Ultrastructural analysis of βII-cKOhearts by TEM showed fragmented cardiac dyads, dilated jSR and reduced jSR contact with T-tubules. Quantitative RT-PCR showed increased expression of calsequestrin 1 and 2, decreased phospholambam, Ncx and Cacna1c (major Cav1.2 subunit), while Ryr2 , Jph2 , Serca2a are unchanged. Protein expression of NCX was decreased, while expression of CAV1.2, RYR2, CASQ2, and SERCA2A remained unchanged. Furthermore, pressure-induced overload of βII-cKO hearts promoted accelerated heart failure (HF). Conclusions: This is the first demonstration that the βII-spectrin cytoskeletal protein is critically important for maintaining the structural integrity of the cardiac dyad. βII-spectrin loss and the resulting alterations in CRU structure, genes, and protein composition promoting accelerated HF.
Abstract 14076: Myocardial Tissue Characterization and Strain by Cardiac Magnetic Resonance and Their Relationship in Pediatric Patients With Acute Myocarditis Within 2 Weeks of Presentation
Authors: Danish Vaiyani, Matthew A Harris, Kevin K Whitehead, Andrea L Jones, David M Biko, Sara L Partington, Kathryn M Restaino, Kimberly Y Lin, Mark A Fogel
Journal: Circulation (2022)

Introduction: Cardiac magnetic resonance (CMR) provides rich data on myocardial function, including indices such as strain, as well as tissue characterization. There is no published data on these values within 2 weeks of the diagnosis of myocarditis. We sought to describe these findings in children with acute myocarditis who underwent CMR early after presentation and determine relationships between these values. Methods: We retrospectively reviewed the clinical and imaging data of patients &lt;21 years clinically diagnosed with acute myocarditis and underwent CMR within 14 days of presentation. Those who suffered cardiac arrest or with autoimmune disease, known cardiomyopathy or congenital heart disease were excluded. Strain was measured using CMR feature tracking. Spearman’s correlation was utilized. Significance was P &lt;0.05. Results: 85 patients underwent CMR at a median of 2 days following presentation (IQR 2 - 4) with median age 16.3 years (IQR 14.3, 17.5). Tissue characteristics, ventricular function and strain are listed in Table 1. 77 studies (90.6%) met Lake Louise criteria for myocarditis and 66 (77.7%) showed late gadolinium enhancement. Global circumferential (GCS) and longitudinal strain correlated with T2 values, biventricular ejection fractions, and peak brain natriuretic peptide (BNP); GCS also correlated with T1 values (Table 1, Figure 1). Conclusions: We present the first data on early strain and tissue characterization for myocarditis. Both global longitudinal and circumferential strain correlated with tissue characteristics and serum measures of acute injury. Strain imaging may be a sensitive marker of myocardial injury in patients with myocarditis.
<i>Notes from the Field:</i> Comparison of COVID-19 Mortality Rates Among Adults Aged ≥65 Years Who Were Unvaccinated and Those Who Received a Bivalent Booster Dose Within the Preceding 6 Months — 20 U.S. Jurisdictions, September 18, 2022–April 1, 2023
Authors: Amelia G. Johnson, Lauren Linde, Amanda B. Payne, Akilah R. Ali, Vanessa Aden, Brandy Armstrong, Brett Armstrong, Steven Auche, Nagla S. Bayoumi, Sarah Bennett, Rachelle Boulton, Carolyn Chang, Abigail Collingwood, Kevin Cueto, Sherri L. Davidson, Yi Du, Aaron Fleischauer, Victoria Force, Darren Frank, Ross Hamilton, Kaitlin Harame, Pauline Harrington, Liam Hicks, Jeffrey D. Hodis, Mikhail Hoskins, Amanda Jones, FNU Kanishka, Ramandeep Kaur, Samantha Kirkendall, Saadiah I. Khan, Anna Klioueva, Ruth Link-Gelles, Shelby Lyons, Joshua Mansfield, Amanda Markelz, John Masarik, Erica Mendoza, Keeley Morris, Enaholo Omoike, Sai Paritala, Komal Patel, Melissa Pike, Xandy Peterson Pompa, Kevin Praetorius, Nadine Rammouni, Hilda Razzaghi, Alexa Riggs, Minchan Shi, Nekabari Sigalo, Emma Stanislawski, Buddhi P. Tilakaratne, Kathryn A. Turner, Caleb Wiedeman, Benjamin J. Silk, Heather M. Scobie
Journal: MMWR Morbidity and Mortality Weekly Report (2023)
Abstract 13763: Institutional Variation of Transcatheter Edge to Edge Repair for Mitral Regurgitation and Short-Term Outcome: A Report From National Readmission Database
Authors: Satoshi Shoji, Toshiki Kuno, Alexandros Briasoulis, Taku Inohara, Shun Kohsaka, Aaqib H Malik
Journal: Circulation (2022)

Introduction: Transcatheter edge-to-edge repair (TEER) of the mitral valve has become an established therapy for patients with severe mitral regurgitation; however, the impact of institutional variations in the number of edge-to-edge TEER for readmission rates with large-scale data is not well investigated. Objectives: Our study aimed to describe the institutional variations of TEER, and also the association between the institutional volume and readmission rates after the procedure across the US institutions. Methods: We conducted a retrospective cohort study of TEER performed in the US between 2019 using the Nationwide Readmission Database. We divided the patients according to the tertiles based on site-specific case of TEER (Q1 [lowest]-Q3 [highest]) and evaluated its association with 30-day readmission rates using Cox proportional hazard model. Results: Overall, 4,922 patients who underwent TEER (mean age 76.8 ± 11.5 years, and 54.5% male) at 250 institutions were included in the analyses. Patients in Q3 (highest tertile) were more likely to be older, and have comorbidities, albeit risk adjusted 30-day readmission rates were similar in each group (Q1: 13.5%; Q2: 13.6%; Q3: 13.7%). Rather than the volume of the procedure, institutional characteristics, such as teaching hospitals located in metropolitan area (hazard ratio [HR 1.92, confidence interval [CI] 1.41-2.61) and institutions with predominantly non-elective (e.g. urgent or emergent) TEER cases (HR 1.75 95% CI 1.39-2.22), or patient characteristics such as chronic heart failure (HR 1.91 95%CI 1.33-2.73), cancer (HR 1.87 95%CI 1.15-3.06), chronic kidney disease (HR 1.45 95% CI 1.20-1.75), chronic pulmonary disease (HR 1.40 95% CI 1.13-1.72), diabetes mellitus (HR 1.39 95% CI 1.12-1.72), and history of percutaneous coronary intervention (HR 1.37 95% CI 1.07-1.76) were associated with a higher incidence of 30-day readmission. Conclusions: Among patients undergoing TEER in a contemporary representative US cohort, procedure volume variation was not associated with the 30-day readmission rate.
Abstract 13062: In vivo Knockdown of Proapoptotic Mir-320 Restores Cardiac Function and Angiogenesis in a Mouse Model of Type 2 Diabetes
Authors: Nilanjan Ghosh, Sonya Fenton, Aniruddha Chatterjee, Daryl Schwenke, Rajesh Katare
Journal: Circulation (2022)

Background: Non-ischemic diabetic heart disease (NiDHD) is characterised by diastolic dysfunction and decreased or preserved systolic function, eventually resulting in heart failure. The fundamental mechanisms leading to NiDHD are still not known. microRNAs (miRNAs) plays a significant role in the development of NiDHD. Objective: To investigate the pathological role of cardiomyocyte enriched pro-apoptotic miR-320 in the development of NiDHD and to determine if therapeutic knockdown of miR-320 can restore impaired cardiac function and angiogenesis in the diabetic heart. Methods and Results: Cardiac tissue were collected from type-2 diabetic individuals undergoing cardiac surgery showed marked upregulation of miR-320, which was associated with downregulation of its direct target pro-survival insulin growth factor-1 (IGF-1) and anti-apoptotic protein Bcl-2. Analysis of cardiac tissue samples collected from type 2 diabetic mice (BKS.Cg-m+/+Leprdb/J) every 4wks, from 8 to 32wks of age showed activation of miR-320 and downregulation of IGF-1 at the later stages of diabetes. To determine if therapeutic knockdown of miR-320 is beneficial, high glucose cultured adult cardiomyocytes were treated with either locked nucleic acid (LNA) anti-precursor (pre)-miR-320 or scrambled (Scr) sequence. Results showed that LNA-anti-pre-320 significantly restored IGF-1 expression and reduced apoptotic cells death (3.1±05 in Scr vs 1.3±0.6 in LNA-anti-pre-320, P&lt;0.01). Finally, to confirm if the effect can be translated in vivo , 24 weeks old type 2 diabetic mice with established systolic dysfunction were injected with LNA-anti-pre-320 once a week for 4wks. Echocardiography confirmed significant restoration of diastolic function and partial restoration of systolic function. Molecular analysis showed marked reduction in miR-320 expression, which was associated with recovery of IGF-1 and Bcl-2. Further, histological analysis confirmed improved angiogenesis and reduced fibrosis in the LNA-anti-pre-320 treated group. Conclusion: miR-320 is a late responding miRNA that aggravates apoptosis and cardiac dysfunction in diabetic heart, and that therapeutic knockdown of miR-320 is beneficial in partially restoring the deteriorated cardiac function.